Generalizing the effectiveness of pharmaceutical promotional expenditures

We perform a meta-analysis to formulate generalizations on the effectiveness of pharmaceutical promotional instruments. A literature search on this topic yields 58 usable (published and unpublished) sources documenting 781 effects. We investigate different direct-to-physician (DTP) and direct-to-consumer (DTC) instruments and study whether and how moderator variables influence promotional effectiveness. Pharmaceutical promotional elasticities are modest in size and differ among marketing instruments. In general, DTP elasticities are higher than DTC elasticities, but the relative effectiveness of DTP instruments depends on the disease category. Higher elasticities appear in studies that include price as an independent variable in the models. Studies that account for endogeneity find lower elasticities.

Dear DTCA, Please Don’t Deceive Me, Don’t Play on My Fantasy

Travail créatif / Creative Work

Dear DTCA, Please Don’t Deceive Me, Don’t Play on My Fantasy

Travail créatif / Creative Work

Revisión de la literatura científica sobre publicidad de medicamentos de venta libre y comportamiento del consumidor

El consumo de medicamentos es un asunto que actualmente se ha convertido en una preocupación a nivel global, ya que no todos los medicamentos están sujetos a prescripción médica, y esto implica que su consumo dependa de otras fuentes de información, como la publicidad masiva o el consejo de personas legas, entre otros. Esta revisión se basó en la publicidad y el impacto que tiene esta frente al consumidor. La presente revisión se dividió en dos categorías dado la relevancia del tema, en la primera se encuentra las características de los medicamentos de venta libre donde se evidenció cómo funciona el sector de la industria farmacéutica, las características de los medicamentos en general y los riesgos del abuso de este comportamiento. Así mismo, en la segunda categoria se habló sobre la publicidad y mercadeo de ventas libres donde se evidenció el alto impacto que tiene la publicidad en el consumidor, las restricciones que hay en el contexto nacional e internacional.

ATTITUDES AND PRACTICES OF GENETIC COUNSELORS IN PROVIDING PREDICTIVE TESTING TO MINORS AT RISK FOR LI-FRAUMENI SYNDROME

Li- Fraumeni Syndrome (LFS) is a rare autosomal dominant hereditary cancer syndrome caused by mutations in the TP53 gene that predisposes individuals to a wide variety of cancers, including breast cancer, soft tissue sarcomas, osteosarcomas, brain tumors, and adrenocortical carcinomas. Individuals found to carry germline mutations in TP53 have a 90% lifetime cancer risk, with a 20% chance to develop cancer under the age of 20. Despite the significant risk of childhood cancer, predictive testing for unaffected minors at risk for LFS historically has not been recommended, largely due to the lack of available and effective screening for the types of cancers involved. A recently developed screening protocol suggests an advantage to identifying and screening children at risk for LFS and we therefore hypothesized that this alongside with the availability of new screening modalities may substantiate a shift in recommendations for predictive genetic testing in minors at risk for LFS. We aimed to describe current screening recommendations that genetic counselors provide to this population as well as explore factors that may have influenced genetic counselors attitude and practice in regards to this issue. An online survey was emailed to members of the National Society of Genetic Counselors (NSGC) and the Canadian Association of Genetic Counsellors (CAGC). Of an estimated 1000 eligible participants, 172 completed surveys that were analyzed. Genetic counselors in this study were more likely to support predictive genetic testing for this population as the minor aged (p

Az online-fogyasztói elégedettség mérésére alkalmas skála tesztelése és véglegesítése a vállalati döntéshozók támogatása céljából (Testing and finalizing a scale for measuring online consumer satisfaction to support the companies decision making process)

A versenyképesség, illetve a gazdaságos működés elengedhetetlen feltétele a fogyasztói elégedettség, melynek egyik meghatározó eleme az észlelt és elvárt minőség közti kapcsolat. A minőségi elvárások az internettel, mint napjaink egyik meghatározó csatornájával kapcsolatban is megfogalmazódtak már, így kapott jelentős szerepet az online szolgáltatásminőség meghatározása, illetve ezzel összekapcsolódva az online-fogyasztói elégedettségmérés. A tanulmány célja, hogy szakirodalmi áttekintést nyújtson a témában, és a szakirodalomból ismert E-S-QUAL és E-RecS-QUAL online-fogyasztói elégedettségmérésre szolgáló skálát megvizsgálja, érvényességét a magyar körülmények között letesztelje, és a szükségesnek látszó módosítások elvégzésével egy Magyarországon használható skálát hozzon létre. Az online-fogyasztók elégedettségmérésének alapjaként az online szolgáltatásminőség fogyasztói érzékelésével, illetve értékelésével kapcsolatos elméleteket járja körbe a tanulmány, és ezután kerül sor a különböző mérési módszerek bemutatására, kiemelt szerepet szánva az E-S-QUAL és E-RecS-QUAL skálának, mely az egyik leginkább alkalmazott módszernek számít. Az áttekintés középpontjában azok a honlapok állnak, melyeken vásárolni is lehet, a kutatást pedig az egyik jelentős hazai online könyvesbolt ügyfélkörében végeztem el. ______ Over the last decade the business-to-consumer online market has been growing very fast. In marketing literature a lot of studies have been created focusing on understanding and measuring e-service quality (e-sq) and online-customer satisfaction. The aim of the study is to summarize these concepts, analyse the relationship between e-sq and customer’s loyalty, which increases the competitiveness of the companies, and to create a valid and reliable scale to the Hungarian market for measuring online-customer satisfaction. The base of the empirical study is the E-S-QUAL and its second scale the E-RecS-QUAL that are widely used multiple scales measuring e-sq with seven dimensions: efficiency, system availability, fulfilment, privacy, responsiveness, compensation, and contact. The study is focusing on the websites customers use to shop online.

Genetic Predictors Of Long-term Response To Growth Hormone (gh) Therapy In Children With Gh Deficiency And Turner Syndrome: The Influence Of A Socs2 Polymorphism.

There is great interindividual variability in the response to GH therapy. Ascertaining genetic factors can improve the accuracy of growth response predictions. Suppressor of cytokine signaling (SOCS)-2 is an intracellular negative regulator of GH receptor (GHR) signaling. The objective of the study was to assess the influence of a SOCS2 polymorphism (rs3782415) and its interactive effect with GHR exon 3 and -202 A/C IGFBP3 (rs2854744) polymorphisms on adult height of patients treated with recombinant human GH (rhGH). Genotypes were correlated with adult height data of 65 Turner syndrome (TS) and 47 GH deficiency (GHD) patients treated with rhGH, by multiple linear regressions. Generalized multifactor dimensionality reduction was used to evaluate gene-gene interactions. Baseline clinical data were indistinguishable among patients with different genotypes. Adult height SD scores of patients with at least one SOCS2 single-nucleotide polymorphism rs3782415-C were 0.7 higher than those homozygous for the T allele (P < .001). SOCS2 (P = .003), GHR-exon 3 (P= .016) and -202 A/C IGFBP3 (P = .013) polymorphisms, together with clinical factors accounted for 58% of the variability in adult height and 82% of the total height SD score gain. Patients harboring any two negative genotypes in these three different loci (homozygosity for SOCS2 T allele; the GHR exon 3 full-length allele and/or the -202C-IGFBP3 allele) were more likely to achieve an adult height at the lower quartile (odds ratio of 13.3; 95% confidence interval of 3.2-54.2, P = .0001). The SOCS2 polymorphism (rs3782415) has an influence on the adult height of children with TS and GHD after long-term rhGH therapy. Polymorphisms located in GHR, IGFBP3, and SOCS2 loci have an influence on the growth outcomes of TS and GHD patients treated with rhGH. The use of these genetic markers could identify among rhGH-treated patients those who are genetically predisposed to have less favorable outcomes.

European collaborative study of early-onset bipolar disorder: Evidence for genetic heterogeneity on 2q14 according to age at onset.

Bipolar disorder has a genetic component, but the mode of inheritance remains unclear. A previous genome scan conducted in 70 European families led to detect eight regions linked to bipolar disease. Here, we present an investigation of whether the phenotypic heterogeneity of the disorder corresponds to genetic heterogeneity in these regions using additional markers and an extended sample of families. The MLS statistic was used for linkage analyses. The predivided sample test and the maximum likelihood binomial methods were used to test genetic homogeneity between early-onset bipolar type I (cut-off of 22 years) and other types of the disorder (later onset of bipolar type I and early-onset bipolar type II), using a total of 138 independent bipolar-affected sib-pairs. Analysis of the extended sample of families supports linkage in four regions (2q14, 3p14, 16p23, and 20p12) of the eight regions of linkage suggested by our previous genome scan. Heterogeneity testing revealed genetic heterogeneity between early and late-onset bipolar type I in the 2q14 region (P = 0.0001). Only the early form of the bipolar disorder but not the late form appeared to be linked to this region. This region may therefore include a genetic factor either specifically involved in the early-onset bipolar type I or only influencing the age at onset (AAO). Our findings illustrate that stratification according to AAO may be valuable for the identification of genetic vulnerability polymorphisms.

KRAS mutation testing for predicting response to anti-EGFR therapy for colorectal carcinoma: proposal for an European quality assurance program.

Novel therapeutic agents targeting the epidermal growth factor receptor (EGFR) have improved outcomes for patients with colorectal carcinoma. However, these therapies are effective only in a subset of patients. Activating mutations in the KRAS gene are found in 30-40% of colorectal tumors and are associated with poor response to anti-EGFR therapies. Thus, KRAS mutation status can predict which patient may or may not benefit from anti-EGFR therapy. Although many diagnostic tools have been developed for KRAS mutation analysis, validated methods and standardized testing procedures are lacking. This poses a challenge for the optimal use of anti-EGFR therapies in the management of colorectal carcinoma. Here we review the molecular basis of EGFR-targeted therapies and the resistance to treatment conferred by KRAS mutations. We also present guideline recommendations and a proposal for a European quality assurance program to help ensure accuracy and proficiency in KRAS mutation testing across the European Union.

Mucoviscidose: illustration de la complexité du dépistage génétique. [The example of cystic fibrosis to highlight the complexity of genetic screening].

Différentes organisations et différents pays aboutissent souvent à des conclusions différentes quant à la pertinence d'introduire un test de dépistage génétique dans la population générale. Cet article décrit la complexité du dépistage basé sur des tests génétiques. Utilisant l'exemple de la mucoviscidose - pour laquelle un groupe de travail national est en train d'évaluer la pertinence d'un dépistage génétique - les auteurs relèvent les situaions où les recommandations de dépistage sont parfois basées sur l'émergence de nouvelles technologies (par exemple, test génétique) et d'opinion publique plutôt que sur la base d'évidences. Ils présentent également les enjeux éthiques et économiques du dépistage génétique de la mucoviscidose. [Abstract] Various institutions and countries often reach different conclusions about the utility of introducing a newborn screening test in the general population. This paper highlights the complexity of population screening including genetic tests. Using the example of cystic fibrosis genetic screening, for which a Swiss Working Group for Cystic Fibrosis is currently evaluating the pertinence, we outline that screening recommendations are often based more on expert opinion and emerging new technologies rather than on evidence. We also present some ethical and economic issues related to cystic fibrosis genetic screening.

Contribution of genetic background, traditional risk factors, and HIV-related factors to coronary artery disease events in HIV-positive persons.

BACKGROUND: Persons infected with human immunodeficiency virus (HIV) have increased rates of coronary artery disease (CAD). The relative contribution of genetic background, HIV-related factors, antiretroviral medications, and traditional risk factors to CAD has not been fully evaluated in the setting of HIV infection. METHODS: In the general population, 23 common single-nucleotide polymorphisms (SNPs) were shown to be associated with CAD through genome-wide association analysis. Using the Metabochip, we genotyped 1875 HIV-positive, white individuals enrolled in 24 HIV observational studies, including 571 participants with a first CAD event during the 9-year study period and 1304 controls matched on sex and cohort. RESULTS: A genetic risk score built from 23 CAD-associated SNPs contributed significantly to CAD (P = 2.9 × 10(-4)). In the final multivariable model, participants with an unfavorable genetic background (top genetic score quartile) had a CAD odds ratio (OR) of 1.47 (95% confidence interval [CI], 1.05-2.04). This effect was similar to hypertension (OR = 1.36; 95% CI, 1.06-1.73), hypercholesterolemia (OR = 1.51; 95% CI, 1.16-1.96), diabetes (OR = 1.66; 95% CI, 1.10-2.49), ≥ 1 year lopinavir exposure (OR = 1.36; 95% CI, 1.06-1.73), and current abacavir treatment (OR = 1.56; 95% CI, 1.17-2.07). The effect of the genetic risk score was additive to the effect of nongenetic CAD risk factors, and did not change after adjustment for family history of CAD. CONCLUSIONS: In the setting of HIV infection, the effect of an unfavorable genetic background was similar to traditional CAD risk factors and certain adverse antiretroviral exposures. Genetic testing may provide prognostic information complementary to family history of CAD.

Genetic associations of visual scores with subsequent rebreeding and days to first calving in Nellore cattle

Records of Nellore animals born from 1990 to 2006 were used to estimate genetic correlations of visual scores at yearling (conformation, C; finishing precocity, P; and muscling, M) with primiparous subsequent rebreeding (SR) and days to first calving (DC), because the magnitude of these associations is still unknown. Genetic parameters were estimated by multiple-traits Bayesian analysis, using a nonlinear (threshold) animal models for visual scores and SR and a linear animal models for weaning weight (WW) and DC. WW was included in the analysis to account for the effects of sequential selection. The posterior means of heritabilities estimated for C, P, M, SR and DC were 0.24 +/- 0.01, 0.31 +/- 0.01, 0.30 +/- 0.01, 0.18 +/- 0.02 and 0.06 +/- 0.02, respectively. The posterior means of genetic correlations estimated between SR and visual scores were low and positive, with values of 0.09 +/- 0.02 (C), 0.19 +/- 0.03 (P) and 0.18 +/- 0.05 (M). on the other hand, negative genetic correlations were found between DC and C (-0.11 +/- 0.09), P (-0.19 +/- 0.09) and M (-0.16 +/- 0.09). The primiparous rebreeding trait has genetic variability in Nellore cattle. The genetic correlations between visual scores, and SR and DC were low and favourable. The genetic changes in C, P and M were 0.02, 0.03 and 0.03/year, respectively. For SR and DC, genetic trends were 0.01/year and -0.01 days/year, respectively, indicating that the increase in genetic merit for reproductive traits was small over time. Direct selection for visual scores together with female reproductive traits is recommended to increase the fertility of beef cows.

Influence of data structure on the estimation of the additive genetic direct and maternal covariance for early growth traits in Nellore cattle

The objective of the present study was to investigate the effect of data structure on estimated genetic parameters and predicted breeding values of direct and maternal genetic effects for weaning weight (WW) and weight gain from birth to weaning (BWG), including or not the genetic covariance between direct and maternal effects. Records of 97,490 Nellore animals born between 1993 and 2006, from the Jacarezinho cattle raising farm, were used. Two different data sets were analyzed: DI_all, which included all available progenies of dams without their own performance; DII_all, which included DI_all + 20% of recorded progenies with maternal phenotypes. Two subsets were obtained from each data set (DI_all and DII_all): DI_1 and DII_1, which included only dams with three or fewer progenies; DI_5 and DII_5, which included only dams with five or more progenies. (Co)variance components and heritabilities were estimated by Bayesian inference through Gibbs sampling using univariate animal models. In general, for the population and traits studied, the proportion of dams with known phenotypic information and the number of progenies per dam influenced direct and maternal heritabilities, as well as the contribution of maternal permanent environmental variance to phenotypic variance. Only small differences were observed in the genetic and environmental parameters when the genetic covariance between direct and maternal effects was set to zero in the data sets studied. Thus, the inclusion or not of the genetic covariance between direct and maternal effects had little effect on the ranking of animals according to their breeding values for WW and BWG. Accurate estimation of genetic correlations between direct and maternal genetic effects depends on the data structure. Thus, this covariance should be set to zero in Nellore data sets in which the proportion of dams with phenotypic information is low, the number of progenies per dam is small, and pedigree relationships are poorly known. (c) 2012 Elsevier B.V. All rights reserved.

Genetic analysis of visual scores and their relationships to mature female weight in Nellore breed

Dados de 79.884 animais da raça Nelore foram utilizados para estimar parâmetros genéticos e avaliar as relações entre os escores de conformação, precocidade e musculatura obtidos à desmama e ao sobreano e o peso das fêmeas à idade adulta. Utilizou-se o método da máxima verossimilhança restrita, em análise multicaracterísticas, com modelo que incluiu os efeitos genéticos aditivos direto e residual, como aleatórios, e os efeitos fixos de grupo de contemporâneos e, como covariáveis, a idade do animal à pesagem e a idade da mãe ao parto (exceto para o peso das fêmeas à idade adulta). Os grupos contemporâneos à desmama foram definidos pelas variáveis: sexo, rebanho, ano e mês de nascimento, grupo de manejo ao nascimento e à desmama. Na definição de grupo contemporâneo ao sobreano também foi incluída a variável grupo de manejo ao sobreano. Para o peso das fêmeas à idade adulta, o grupo de contemporâneos foi composto por rebanho, ano de nascimento, grupo de manejo ao sobreano, ano e estação da pesagem. Os efeitos genético materno e de ambiente permanente materno também foram incluídos no modelo para análise dos escores de conformação, precocidade e musculatura à desmama. As estimativas de herdabilidade direta obtidas foram 0,18 ± 0,02 para o escore de conformação; 0,21 ± 0,01 para o escore de precocidade; 0,22 ± 0,01 para o escore de musculatura à desmama e 0,24 ± 0,01 para o escore de conformação; 0,27 ± 0,01 para o escore de precocidade; e 0,26 ± 0,01 para o escore de musculatura ao sobreano e 0,42 ± 0,02 para o peso das fêmeas à idade adulta. As correlações genéticas estimadas entre os escores visuais medidos à desmama e ao sobreano foram positivas, variando de média a alta magnitude (0,56 ± 0,03 a 0,85 ± 0,01). Por outro lado, as correlações genéticas estimadas entre os escores visuais e o peso das fêmeas à idade adulta foram positivas e moderadas, variando de 0,21 ± 0,03 a 0,35 ± 0,03. Os resultados obtidos indicam que a seleção de animais com maiores escores visuais, principalmente ao sobreano, deve promover aumento do peso das fêmeas à idade adulta.

USE OF PROGENY TESTING IN BEEF-CATTLE - PREDICTION OF GENETIC GAIN IN A NELORE CATTLE-BREEDING PROGRAM

Genetic gains predicted for selection, based on both individual performance and progeny testing, were compared to provide information to be used in implementation of progeny testing for a Nelore cattle breeding program. The prediction of genetic gain based on progeny testing was obtained from a formula, derived from methodology of Young and weller (J. Genetics 57: 329-338, 1960) for two-stage selection, which allows prediction of genetic gain per generation when the individuals under test have been pre-selected on the basis of their own performance. The application of this formula also allowed determination of the number of progeny per tested bull needed to maximize genetic gain, when the total number of tested progeny is limited.